Abstract
Cathepsin K (Cat K) is the primary enzyme involved in Type I collagen degradation in bone resorption. The development of a Cat K inhibitor should provide an effective treatment for osteoporosis. Key components of a clinically viable inhibitor are oral bioavailability, high selectivity over related cathepsins, and a covalent, reversible warhead to bind to the active site cysteine of the enzyme. This article reviews recent advances in the design of inhibitors derived from peptidic leads that contain either a ketone or nitrile electrophile. Three of these compounds have progressed into clinical trials and one, odanacatib (5), is currently in Phase III studies for the treatment of post-menopausal osteoporosis.
Keywords: Osteoporosis, cathepsin K, cysteine protease, lysosomotropism, selective inhibitor, peptidomimetic, bone resorption
Current Topics in Medicinal Chemistry
Title: Peptidomimetic Inhibitors of Cathepsin K
Volume: 10 Issue: 7
Author(s): W. Cameron Black
Affiliation:
Keywords: Osteoporosis, cathepsin K, cysteine protease, lysosomotropism, selective inhibitor, peptidomimetic, bone resorption
Abstract: Cathepsin K (Cat K) is the primary enzyme involved in Type I collagen degradation in bone resorption. The development of a Cat K inhibitor should provide an effective treatment for osteoporosis. Key components of a clinically viable inhibitor are oral bioavailability, high selectivity over related cathepsins, and a covalent, reversible warhead to bind to the active site cysteine of the enzyme. This article reviews recent advances in the design of inhibitors derived from peptidic leads that contain either a ketone or nitrile electrophile. Three of these compounds have progressed into clinical trials and one, odanacatib (5), is currently in Phase III studies for the treatment of post-menopausal osteoporosis.
Export Options
About this article
Cite this article as:
Cameron Black W., Peptidomimetic Inhibitors of Cathepsin K, Current Topics in Medicinal Chemistry 2010; 10 (7) . https://dx.doi.org/10.2174/156802610791113450
DOI https://dx.doi.org/10.2174/156802610791113450 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Role of miRNAs in Muscle Stem Cell Biology: Proliferation, Differentiation and Death
Current Pharmaceutical Design Can Wogonin be Used in Controlling Diabetic Cardiomyopathy?
Current Pharmaceutical Design Patent Selections
Recent Patents on Cardiovascular Drug Discovery Editorial [Bioengineering and Clinical Perspectives in Diagnostic and Therapeutic Applications of Microbubbles (Executive Guest Editor: Theodore G. Papaioannou)]
Current Pharmaceutical Design The Importance of Lost Minerals in Heart Failure
Cardiovascular & Hematological Agents in Medicinal Chemistry Restriction Factors Against Recombinant Adeno-associated Virus Vectormediated Gene Transfer in Dystrophin-deficient Muscles
Current Gene Therapy MicroRNA-34a Promotes Cardiomyocyte Apoptosis Post Myocardial Infarction Through Down-regulating Aldehyde Dehydrogenase 2
Current Pharmaceutical Design Insulin- and Growth Factor-Resistance Impairs Vascular Regeneration in Diabetes Mellitus
Current Vascular Pharmacology Hemolytic Uremic Syndrome in Children
Current Pediatric Reviews Sweet and Sour - Oxidative and Carbonyl Stress in Neurological Disorders
CNS & Neurological Disorders - Drug Targets An Emerging Antiarrhythmic Target: Late Sodium Current
Current Pharmaceutical Design Cell Sheet Technology for Heart Failure
Current Pharmaceutical Biotechnology Epigenetic Regulation of Myocardial Homeostasis, Self-Regeneration and Senescence
Current Drug Targets Adult Stem Cells and Skeletal Muscle Regeneration
Current Gene Therapy Pharmacokinetic Considerations of Perinatal Antiretroviral Therapy
Current Drug Metabolism Imaging of Visceral Adipose Tissue: An Emerging Diagnostic Tool and Therapeutic Target
Current Drug Targets - Cardiovascular & Hematological Disorders SIRT1 as a Promising Novel Therapeutic Target for Myocardial Ischemia Reperfusion Injury and Cardiometabolic Disease
Current Drug Targets Disruption of Circadian Rhythms and Sleep on Critical Illness and the Impact on Cardiovascular Events
Current Pharmaceutical Design Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy
Current Pharmaceutical Design Statins Attenuate Fibrotic Manifestations of Cardiac Tissue Damage
Current Molecular Pharmacology